Adapting Cancer Immunotherapy Models for the Real World

Abstract

Early experiments in mice predicted the success of checkpoint blockade immunotherapy in cancer patients. However, these same animal studies failed to accurately predict many of the limitations and toxicities of treatment. One of the likely reasons for this discrepancy is the nearly universal use of young healthy mice, which stand in stark contrast to diverse patient populations varying in age, weight, diet and hygiene. Because these variables impact immunity and metabolism, they also influence outcomes during immunotherapy and should be incorporated into the study design of preclinical experiments. Here, we discuss recent findings that highlight how efficacy and toxicity of cancer immunotherapy are affected by patient variation, and how distinct host environments can be better modeled in animal studies.

Tailoring Biomaterials for Cancer Immunotherapy: Emerging Trends and Future Outlook

“…[14,[106][107][108] Tumor-specific T cells may be negatively regulated by inhibitory factors, such as PD-1/PD-L1 and CTLA4, which inhibit the immune response. [14,[106][107][108] Tumor-specific T cells may be negatively regulated by inhibitory factors, such as PD-1/PD-L1 and CTLA4, which inhibit the immune response.…”

Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

“…So while some aspects, such as cell line, strain and sex of mice, number of cells injected, and the injection site of antibody treatment were maintained, others were unknown or not easily controlled for. These include variables such as cell line genetic drift (Hughes et al, 2007; Kleensang et al, 2016), circadian biological responses to therapy (Fu and Kettner, 2013), mouse strain stocks (Clayton and Collins, 2014), housing temperature in mouse facilities (Kokolus et al, 2013), and the obesity and microbiome of recipient mice (Klevorn and Teague, 2016; Macpherson and McCoy, 2015). Additionally, a differential response to immunotherapy can occur due to heterogeneity in individual tumor microenvironments (Grosso and Jure-Kunkel, 2013), which has also been observed in the clinical setting (Ascierto and Marincola, 2014; Stevenson, 2014).…”

Nanomaterials for cancer immunotherapy

“…Due to complicated stromal signaling inside the tumor, reshaping the immune profile of the TME appears to be more effective than the use of cytotoxic drugs directly on tumor cells. Additionally, studies on cancer immunotherapy should pay more attention to tumor categories since different tumor models may have completely different immune cell infiltration statuses or TME immune signatures [279]. …”